Mumps Meningoencephai'tis A Clinical Review of 119 Cases with One Death HENRY B. BRUYN, M.D., HAROLD M. SEXTON. M.D., and HENRY D. BRAINERD, M.D., San Francisco MUMPS IS A generalized, systemic, virus infection in * Mumps is one of the most common viruses to which the salivary glands are commonly affected and affect the central nervous system and should be given primary consideration in the differential in which inflammation of the central nervous system diagnosis of aseptic meningitis. Many cases of occurs with such frequency that it can hardly be mumps infection do not involve the salivary considered a complication. In fact, the virus of glands. mumps could be said to be one of the most common The course of mumps meningoencephalitis is viral agents to affect the central nervous system. De- usually benign, with fever and signs of menin- geal irritation lasting less than five days. The spite the extensive literature attesting these facts, findings in the cerebrospinal fluid are usually there still exists the widespread impression that distinctive, with leukocyte content greater than mumps meningoencephalitis is a rare complication. 200 per milliliter, of which 80 per cent or more Hamilton10 in 1790 presented one of the first for- are lymphocytes. Sequelae, even of a minor na- ture, are rare. mal reports of "A Distemper, By the Common Peo- Death is extremely rare in recorded literature. ple in England Vulgarly Called the Mumps." In this A fatal case of mumps meningoencephalitis is very carefully written report he described the usual described herein. course of this disease and stressed the frequency of central nervous system involvement. It was his opinion that inflammation of the testicles and the tropic quality. Henderson's'1 report of 11 cases of brain was the result of failure of a proper diaphore- clinically apparent central nervous system involve- sis of the affected parts. He described one death due ment in a total of 14 cases of mumps infection, was to this "tumult of the brain." It is interesting that most striking. this author noted that the disease was generally con- It is, however, rather difficult to reconcile the in- fined to young men from the age of puberty to about cidence in 1918-1920 U. S. Army camps of 0.01 per 30 years and stated that he had never seen any cent of clinically apparent mumps meningoencepha. females above ten years of age affected by this litis with the usual 10 to 30 per cent incidence re- illness. -ported since then. It would seem likely that a more A unique feature of mumps is the observation of careful clinical evaluation with the possibility of pleocytosis, as evidence of inflammation of the cen- central nervous symptoms in mind would have raised tral nervous system, unaccompanied by any clinical this incidence rather sharply. Despite such varia- symptpms of encephalitis or meningitis. Monod18 tions it would seem safe to presume that in 30 to 40 was the first to report this symptomless meningo- per cent of cases of mumps infection there will be encephalitis. He noted increased leukocyte content central nervous system involvement with clinical in the spinal fluid of six of eight patients with mumps. symptoms not necessarily apparent. In the literature of the last 50 years there have The exact pathogenesis of this central nervous been a number of investigations of mumps with re- system involvement by the virus has been given ports of the incidence of central nervous system in- consideration since Hamilton,10 over 150 years ago, volvement. Table 1 summarizes a number of these looked upon it as the result of a disturbance of the reports. The rather wide variation in the incidence course of the natural "humors" of the disease. Over of clinically apparent nervous system disease will 40 years ago Dopter6 suggested that the mumps virus be noted. While it is true that the factor of clinical should be considered as being primarily in the judgment modifies data of this type, it is nevertheless meninges rather than to "consider the meningitis as rather hard to escape the conclusion that the virus a complication." His study of a large number of may vary from one epidemic to the next in neuro- cases of mumps is summarized in Table 1. Some 20 years ago Philibert2l restated the belief, From the Departments of Pediatrics and Medicine, University of on the basis of the frequency of the occurrence of California School of Medicine, San Francisco 22. and the Infectious Disease Laboratory of the San Francisco Hospital, San Francisco 10. pleocytosis, that the virus of mumps was primarily Presented before a Joint Meeting of the Sections on Public Health, neurotropic. He felt that the disease might be pri- Pediatrics, and General Practice at the 85th Annual Session of the California Medical Association, Los Angeles, April 29 to May 2, 1956. marily one of the central nervous system, as illus- VOL. 86. NO. 3 * MARCH 1957 153 TABLE 1.-Incidence of Meningoencephallfts In Mumps, Clinically Apparent or Inapparent, as Summarized from Published Investigations Total Incidence Clinically Total Central Cases Apparent Inapparent Incidence Authors Year Studied (Per Cent) (Per Cent) (Per Cent) Dopter6... 1910 1,705 10 U. S. Army Medical Department (Wesselhoeft25 data) 1918-20 9,690 0.01 Silwer22 .1936 30 .... 10 Greene and Heeren6 -1937 100 11 Finkelstein7. 1938 40 25 15 40 Frankland8 1941 234 30 . Bang and Bang2 .......... .1943 371 29 36 65 McGuinness and Gall17....................................1944 1,378 4 Steinberg23 1944 165 10 Holden, Eagles and Stevens14.--------------------------.....----.-1946 100 33 8 41 Laurence and McGavin1 .. 1948 235 4 Hendersonl ----------------- . 1952 14 78 Bowers and Weatherhead3 . ... 1953 250 25 trated in several cases which he reported in which a diagnosis of encephalitis of unknown origin, or meningitis preceded parotid gland involvement. septic meningitis. In the earlier years of the period These early hypotheses received eventual confir- covered by this study, the importance and frequency mation in the isolation and identification of the of central nervous system involvement in mumps was mumps virus from cerebrospinal fluid. Swan and not fully appreciated and several of the patients Mawson,24 in 1943, accomplished the isolation of the whose cases are reported herein were discharged virus from pooled saliva as well as from cerebro- with a diagnosis of encephalitis of unknown origin, spinal fluid inoculated into the parotid glands of as well as infectious parotitis. The criteria for attrib- rhesus monkeys. Later, in 1947, Henle and McDou- uting central nervous system disease to mumps virus gall12 isolated the mumps virus from the cerebro- were: (1) parotitis or other salivary gland involve- spinal fluid taken on the second day of disease and ment typical of mumps; or (2) a significant rise of injected into the amniotic fluid of fertile hens' eggs either hemagglutination inhibition antibody or com- that had been in incubation for eight days. The virus plement fixing antibody. Also included in the series was identified by specific hemagglutination tests. It were three cases, before 1948, in which the clinical is now well accepted that such virus isolation from manifestations of central nervous system disease re- cerebrospinal fluid is easily done by this method. sembled those of mumps meningoencephalitis and in It would thus seem that the central nervous system which a history of exposure and compatible incuba- is directly involved with mumps virus invasion and. tion period for mumps was well established. that the signs, symptoms and laboratory findings are Serological tests were performed after 1948 at the not of a nonspecific type sometimes found in other Infectious Disease Laboratory of the San Francisco viral diseases. Hospital or at the State of California Department of The present study, a review of 119 cases of mumps Public Health Viral and Rickettsial Disease Labora- meningoencephalitis in patients who were cared for tory. Central nervous system involvement in this at the San Francisco Hospital, is presented in order series of cases was invariably clinically apparent to stress not only the frequency of such manifesta- with obvious signs of meningeal irritation. In most tions of mumps virus infection but also to review cases, lumbar puncture was done and the finding of briefly the clinical features and the typical laboratory more than 10 leukocytes per milliliter of cerebro- findings. A single fatal case will be presented in spinal fluid was considered abnormal. In a few in- detail because of the rarity of this result and the stances, the observation of signs of meningeal in- lack of detailed pathological findings available in volvement accompanying parotitis was considered the recorded literature. sufficient to establish the clinical diagnosis without examination of cerebrospinal fluid. MATERIAL AND METHODS All the patients upon which the present investiga- RESULTS tion is based were hospitalized on the isolation ward of the San Francisco Hospital in the 12-year period During the 12 years covered by the present study 1943-1955. All were observed by one of the present there was a total of 119 cases at San Francisco investigators. Records were studied in which the Hospital that met the criteria set down for the diag- diagnoses at the time of discharge included mumps nosis of mumps meningoencephalitis. Data on the or infectious parotitis, as well as records including number of cases of mumps each year in San Fran- 154 CALIFORNIA MEDICINE cisco and the number of patients with mumps men- TABLE 2.-Mumps MeningoencephalitMs at San Francisco Hospital ingoencephalitis admitted to San Francisco Hospital Cases of are given in Table 2. The number of patients with Mumps Parotitis Total Reported in CNS* CNS only CNS central nervous system involvement admitted to the Year San Francisco (SFH)t (SFH) (SFH) hospital bore no relationship to the total number of 1943 ....